Support Care Cancer (2015) 23:2843–2851
DOI 10.1007/s00520-015-2827-1
REVIEW ARTICLE
A state-of-the-art review of the management and treatment
of taste and smell alterations in adult oncology patients
Trina Thorne 1,4 & Karin Olson 2 & Wendy Wismer 3
Received: 24 March 2015 / Accepted: 16 June 2015 / Published online: 11 July 2015
# Springer-Verlag Berlin Heidelberg 2015
Abstract
Purpose The purpose of this review was to examine studies of
interventions for the prevention and management of taste and
smell alterations (TSA) experienced by adult oncology
patients.
Methods Articles published between 1993 and 2013 were
identified by searching CINAHL, MEDLINE and Food Sci-
ence & Technology Abstracts (FSTA) and were included if
they were in English and focused on adult oncology patients.
Only interventions within the scope of nursing practice were
reviewed.
Results Twelve articles were identified for inclusion. Four
research groups examined zinc supplementation, with two
claiming that zinc supplementation was an effective interven-
tion and two claiming it had no effect on TSA. The remaining
research groups examined eight other interventions, with
varying results. Marinol, megestrol acetate and Synsepalum
dulcificum interventions appear promising.
Conclusion Based on this review, there does not yet appear to
be an effective approach for preventing or managing TSA in
adult oncology patients. Although some interventions show
* Trina Thorne
trina.thorne@covenanthealth.ca
1
University of Alberta, Edmonton, Alberta, Canada
2
Faculty of Nursing, University of Alberta, 4-359 ECHA, 11405 87
Avenue, Edmonton, Alberta T6G 1C9, Canada
3
Department of Agriculture, Food and Nutritional Science, University
of Alberta, 3-18C Agriculture/Forestry Ctr, Edmonton, Alberta T6G
2P5, Canada
4
Youville Home, 9A St. Vital Avenue, St. Albert, Alberta T8N 1K1,
Canada
promise, further research is necessary to determine their
efficacy.
Keywords Taste . Smell . Dysgeusia . Chemosensory .
Neoplasm . Cancer
Introduction
Taste dysfunction in patients living with cancer is a complex
problem and is associated with alterations in smell [1]. Re-
search, assessment and development of effective interventions
will be necessary to offer supportive or preventive care. In this
review, we summarize literature about the treatment and man-
agement of taste and smell alterations (TSA) in adult oncology
patients.
TSAs are common and can be the result of the disease or
treatment [2]. Mainly related to cell damage, TSAs can be the
result of altered cell structure, receptor surface changes, inter-
ruption in neural coding or a decrease in the number of normal
cells [3]. Hutton et al. found that 86 % of patients with ad-
vanced cancer reported chemosensory abnormality [4]. The
most common complaints were persistent bad taste, taste dis-
tortion and heightened sensitivity to odours. Patients with se-
vere chemosensory complaints showed lower energy intakes,
higher weight loss and lower quality of life scores than pa-
tients with mild or moderate chemosensory complaints [4].
Food flavours and aromas enhance the feelings of satiety
and pleasure from meals and are primary reinforcers of eating;
sensory stimulation derived from food is important in patients
with cancer, as other sources of gratification may be less avail-
able [5]. Alterations in taste are distressing for patients and can
lead to food aversions, reduced food intake and nutritional
deficits [2]. Anorexia is common among people who experi-
ence TSAs and related changes in food preference [6].
2844
Treatment side effects that impair sensory organs affect the
ability to interact with the environment, which can be
distressing to patients [1]. Because smell and taste are linked,
and both are required for the sensation of flavour, changes to a
patient’s sense of smell can affect food flavour [2]. Although
cancer is reported to be associated with impaired olfactory
function, very few studies have directly evaluated this effect
[5].
Patients rarely address taste alterations, and health care
providers often consider them a side effect that is unavoidable
[7]. In this summary, we identify gaps in knowledge, evaluate
current evidence and formulate suggestions for research to
identify and evaluate interventions for the prevention and
management of TSA in adult oncology patients.
Methodology
This state-of-the-art review [8] was based on a search of liter-
ature indexed in the Food Science & Technology Abstracts
(FSTA), MEDLINE and CINAHL databases. The search
terms: taste, smell, dysgeusia, chemosensory, neoplasm and
cancer yielded 226 articles. English language studies about
TSA published between 1993 and 2013 were selected for
further evaluation (n = 42). The reference lists of these articles
were reviewed for additional sources related to this topic,
yielding an additional 37 articles. Only articles describing in-
terventions within the scope of nursing practice were includ-
ed. Of the 79 articles considered, 12 focused on TSA in adult
oncology patients and included interventions that were within
the scope of nursing practice and were thus included in this
review (see Appendix Table 1).
Results
This review examines evidence on strategies for prevention
and treatment of TSAs. Of the 12 included studies, six tested
supportive TSA interventions [9–14], four tested interventions
to prevent TSA [15–18] and two tested both supportive and
preventive interventions [19, 20]. The primary end point of 11
studies was the effects of the intervention on TSA. The pri-
mary end point of the final study was the efficacy of an inter-
vention on radiotherapy (RT)-induced mucositis; the effect of
this intervention on TSA was a secondary end point [16]. Nine
different interventions were examined.
Zinc supplementation
Zinc sulfate was the only intervention included in multiple
trials. The authors of these studies reported conflicting results.
The specific mechanism of zinc in taste perception is un-
known. As a growth factor and component of the salivary
Support Care Cancer (2015) 23:2843–2851
enzyme carbonic anhydrase VI, zinc contributes to sensory
stem cell stimulation [11]. In the first study, zinc sulfate
(45 mg po tid) appeared to provide benefit to patients [12].
Participants were given zinc sulfate tablets or placebo three
times daily after meals starting with the onset of perceived
TSA. This regime was followed during the course of external
radiotherapy (ERT) and up to 1 month after ERT termination.
Researchers assessed taste acuity by measuring detection and
recognition thresholds using a standard three-stimulus drop
technique for four taste qualities (salty, sweet, sour and bitter
assessed using aqueous solutions of NaCl, saccharose, HCl
and urea, respectively). In this study, the intervention was
considered effective because group threshold differences for
bitter detection and for salt recognition during ERT, as well as
salt, sweet and sour recognition at the end of ERT, were sig-
nificantly lower than the control group, indicating higher taste
acuity. The secondary end points (decline and recovery of
taste acuity) favoured the zinc group, but the differences were
not statistically significant. Zinc sulfate was well tolerated.
A second research group explored the usefulness of IV zinc
(0.33 mg daily) during chemotherapy as a strategy for
preventing TSA [18]. In this study, participants in the exper-
imental group were given parenteral zinc, administered with
chemotherapy. Taste disorder was evaluated using an
electrogustometer. An increase in taste threshold was defined
as the indicator of an adverse alteration in taste. Taste thresh-
old was measured in two different nerve areas before and after
day three and after 1, 2 and 4 weeks of chemotherapy. The
authors reported a statistically significant change in the taste
threshold between the experimental and control group at 2 and
4 weeks (p < 0.05), in the chorda tympani nerve area. Differ-
ences were noted in the glossopharyngeal nerve area at
2 weeks, but were not statistically significant, and there was
no difference in this nerve area at 4 weeks. The authors con-
cluded IV zinc may prevent TSA.
In the third study, participants in the experimental group
(n = 61) were given zinc sulfate tablets (45 mg) three times
daily [20]. Their scores on a previously validated taste ques-
tionnaire and patient-reported taste alterations were used as
measurement tools. The zinc sulfate/placebo was started with-
in 7 days of the initiation of RT and was given for 4 weeks
after RT completion, for a total treatment period of 2 months.
Zinc sulfate administration reduced the median interval to the
appearance of TSA (p = 0.09), but did not improve post-
treatment time to taste recovery compared to the placebo
group (p = 0.16). In this study, zinc sulfate administration
prior to therapy appears to have had a negative effect on the
interval to taste recovery and the authors recommended that
zinc sulfate not be used to treat or prevent TSA.
The most recent trial comparing zinc with placebo for
chemotherapy-related TSA revealed no significant difference
between the use of oral zinc sulfate (220 mg bid) and placebo
[10]. To measure improvement of TSA, a zero-to-100 scale
Support Care Cancer (2015) 23:2843–2851
was used. There was no statistically significant improvement
in loss or distortion of taste or smell with the addition of zinc.
There was a trend toward loss of taste improvement over time
in both groups and a non-significant worsening in loss of
smell over time in the zinc group. These results were consis-
tent with other studies that failed to demonstrate prevention of
TSA with similar doses of zinc.
The studies in favour of zinc supplementation used validat-
ed objective measurement tools and compensated for smaller
sample sizes with appropriate statistical analyses [12, 18]. It is
worth noting that all participants were given standardized
meals and age was identified as a possible confounding vari-
able [18]. Alternatively, the studies that did not support the use
of zinc sulfate had relatively larger samples and relied on
subjective measures to determine group differences [10, 20].
Objective evaluation of taste and smell testing was not used,
but patient report is considered the gold standard in clinical
care [10, 20]. The route of zinc administration and dosing
varied, which may have contributed to the conflicting results.
Megestrol acetate
Megestrol acetate (480 mg daily) was administered daily to
weight-losing patients with advanced cancer experiencing
TSA [19]. Megestrol acetate acts predominantly as a potent
agonist of progesterone receptors to exert its effects [21]. Sub-
jective taste and smell were assessed at baseline and at the 1-,
2- and 3-month points using a non-validated brief question-
naire scored from one to five, according to the degree of the
loss or change for each parameter. Using this instrument, sig-
nificant improvements were seen in loss of taste (p = 0.000)
and smell qualities (p = 0.02) in the megestrol acetate (MA)
group compared to the placebo group after 3 months. Al-
though megestrol acetate did have a statistically significant
positive effect on TSA, there were several methodological
problems with this study. First, the authors changed the tool
used for assessment of TSA part way through the study due to
lack of patient compliance/dissatisfaction [19]. In addition, the
groups were heterogeneous (within and between) in relation to
nutritional supports (p = 0.001, 0.01), age (p = 0.02) and
primary tumour site (p = 0.03). Therefore, it is difficult to
exclude the possibility of confounding variables affecting
the outcome.
Oral glutamine
Cancer patients receiving taxane-based chemotherapy for the
first time were given oral glutamine in an attempt to prevent
TSA [17]. Glutamine is vital in nitrogen transfer between
tissues and synthesis of RNA, DNA, and some neurotransmit-
ters. Patients were randomized to receive oral glutamine (30 g
daily) or placebo (maltodextrin) from day one of chemother-
apy. Dysgeusia was measured with a visual analogue scale.
2845
Objective taste (sour, sweet, salty, bitter recognition) and tox-
icity were also assessed. Daily dysgeusia scores did not differ
between the groups. These results may have been due to the
relatively small sample, with 11 of 41 participants not com-
pleting the trial. Oral glutamine was not effective in reducing
TSA.
Amifostine
Amifostine is a thiophosphate prodrug, which protects normal
organs and tissues from oxidative damage [3, 22]. A prospec-
tive follow-up study of more than 5 years was performed to
determine the preventive effect of amifostine on long-term
chemo-radiotherapy-associated toxicities, including TSA
[15]. Taste was measured using an electrogustometer. Altered
taste was reported by 33 % of patients. Compared to the con-
trol group, loss of taste was significantly lower in the
amifostine group (0.381 versus 0.464, p = 0.04). Amifostine
administration was beneficial in reducing TSA up to 1 year
after treatment, but showed no benefits after that time point.
The large treatment effect and trial duration lend credibility to
this study. Unfortunately, the non-randomized design and the
specific treatment modalities limit the generalizability of the
conclusions [15].
Self-care intervention and patient strategies to manage
taste and smell alterations
Each of the 42 patients participating in the study was given a
taste change suggestion sheet and an educational intervention
[11]. Examples of items on the suggestion sheet included
adding more/using less seasoning, eating bland foods,
avoiding spicy foods and sucking on hard candy. The taste
change survey developed for this study, based on the results
of a large study of 254 patients undergoing chemotherapy, was
used to capture the nature of taste changes, presence of other
symptoms and satisfaction with the suggested strategies. Two
open-ended questions elicited foods patients avoided and ad-
ditional strategies used to manage taste and smell changes.
Initially, patients were eligible to participate if their diagnosis
was lymphoma, breast, lung or ovarian cancer and if they were
receiving doxorubicin, carboplatin, cisplatin or cyclophospha-
mide. The authors felt the strict inclusion criteria affected ac-
crual, and ultimately, any patient with cancer and undergoing
chemotherapy was included. Relationships were found be-
tween types of taste changes experienced and the helpfulness
of particular strategies. For example, patients bothered by a
bitter taste reported avoiding beef and eating smaller meals
more frequently to be more beneficial than patients not both-
ered by bitter taste. Use of a taste change suggestion sheet
encouraged self-care and provided strategies for managing
taste changes that were helpful for the majority of participants.
Although the study was designed to measure patient responses
2846
pre- and post-intervention, no significant differences were
found between time points [11]. The 2-week study interval
may have been too short to determine changes over time. It
is also possible that the suggestion sheet was confusing for
patients, as it included negative and positive strategies. In
addition to this, the authors’ instruments were not validated
and may not have been sufficiently sensitive to capture chang-
es in patient experiences. The results of this study were also
restricted by the small sample size and lack of comparison to a
standard of care group.
Dietary counselling and flavour enhancement
The experimental group was given 13 bottles of various food
flavours and educated on their ability to counteract unpleasant
tastes such as bitter and compensate for TSA [13]. The fla-
vours used were familiar, versatile, natural, sodium free and
non-allergenic (contain no protein). Patients were encouraged
to masticate their food well to increase salivation and release
odorous compounds. Pushing food against the soft palate,
which has many taste buds, was also encouraged. Meal plan-
ning instruction was given, with emphasis on textures and
temperatures. Subjects in both groups were instructed to avoid
certain foods if they had a dry or sore mouth (citrus, spicy).
Taste and odour assessments were measured using a taste and
smell questionnaire, taste threshold testing and olfactory
threshold testing. Detection and recognition thresholds were
determined using an ascending forced-choice method of
limits. The protocol encouraged subjects to amplify the fla-
vour of their foods individually, in order to compensate for
TSA. Control subjects received nutritional information only.
Two taste/odour measures demonstrated a statistically signif-
icant difference between groups [13]. For sucrose detection
thresholds, the experimental group had significantly higher
thresholds than the control group across all time points (p
0.01). Phenethyl alcohol (odour) detection thresholds were
also lower in the experimental group across all time points
(p 0.05). The data collected in the taste and smell question-
naire showed a significant interaction between the experimen-
tal group and time point in relation to self-reported ability to
taste (p < 0.05). At 1 and 3 months, a negligible difference was
seen between groups. However, by the 8-month point, 78 % of
the experimental group reported a good to excellent ability to
taste, compared to 50 % in the control group. The same trend
was seen for perceived ability to smell, although it was not
statistically significant. At the 8-month point, there were no
substantial differences between the experimental and control
groups’ ability to taste, but there were significant differences
in perception of ability. High attrition rates were noted in both
groups, and the results of this study may not be generalizable
to elderly cancer patients, as those who dropped out were
older and in poorer health [13]. The authors collected subjec-
tive and objective data at multiple assessment points,
Support Care Cancer (2015) 23:2843–2851
confirming the combination of flavour enhancement,
chemosensory education and nutritional information may
have a positive effect on TSA.
Bethanechol
The authors performed a secondary analysis of data on
36 patients to evaluate the effect of bethanechol on sal-
ivary gland dysfunction in head and neck cancer pa-
tients receiving RT. Because bethanechol has been
shown to stimulate saliva production, the authors hy-
pothesized that it would prevent taste loss [16]. Oral
bethanechol (25 mg) was administered thrice daily from
the start to the completion of RT to reduce RT-induced
mucositis, candidiasis and TSA. Although not statistical-
ly significant, almost 70 % of the bethanechol group
compared to 95 % of those in the placebo group (arti-
ficial saliva) reported taste loss during RT. There was
no difference between the two groups in the time course
development of taste loss. The authors concluded that
bethanechol did not prevent RT-associated taste loss,
mucositis or candidiasis. Daily timing of bethanechol
with respect to RT was not standardized, and due to
the different formulations of the experimental and pla-
cebo products, it was not possible for the study to be
double blinded. The study should be repeated with a
larger sample size in order to evaluate possible benefits
of bethanechol.
Synsepalum dulcificum (miracle fruit)
Miraculin, a protein in the fruit S. dulcificum, binds to taste
receptors in an acidic environment to generate a sweet sensa-
tion, thus improving the palatability of foods by masking
some unpleasant tastes for a short duration [14]. The study
consisted of a convenience sample of eight patients and used
a crossover design. Miracle fruit or a placebo of dried cran-
berries was consumed immediately prior to meals for 2 weeks.
Both formulations were packaged similarly by the pharmacy.
Participants recorded food and drink intake in daily food dia-
ries and rated taste changes with each food as the same, better
or worse than their previous experience. Participants were also
asked to record if the changes lasted throughout the meal. In
addition to individual food choices, patients were asked to trial
common sour- or bitter-tasting foods such as lemons or grape-
fruit. Study participants who ingested miraculin before meals
reported positive taste changes and some reported increased
food intake compared to the placebo group. The sample size
was too small to be analysed statistically, but the results are
supportive of the hypothesis that miracle fruit is able to reduce
the impact of TSA and make foods more palatable.
Support Care Cancer (2015) 23:2843–2851
Marinol
This was a proof-of-principle study and was intended to pro-
vide direction for future trials [9]. Adult patients with ad-
vanced cancer experiencing TSA were given marinol (delta-
9-tetrahydrocannabinol (THC) 2.5 mg) or a placebo twice
daily, to determine its effect on TSA. THC increases motiva-
tion to eat energy dense foods and enhances food enjoyment
via endocannabinoid receptors that stimulate the orosensory
reward pathway. Multiple tools of assessment were used, in-
cluding a taste and smell survey, 3-day food record, appetite
(SLIM) and macronutrient preference assessments, quality of
life questionnaire (FAACT), Edmonton Symptom Assess-
ment Scale (ESAS) and an interview. After 14 days, the pa-
tients taking marinol had increased protein intake as a propor-
tion of total calories compared to those on placebo.
Chemosensory perception (p < 0.001 to 0.026), appetite
(p = 0.05), relaxation (p = 0.045) and quality of sleep
(P = 0.025) also showed statistically significant improved re-
sponses to marinol. Patients taking marinol were two times
more likely to report Bbetter taste^ than placebo (p = 0.026).
Marinol shows promise and may be useful in treating TSA
and increasing oral intake. The number of assessment tools
reduced the potential for bias. Potential limitations were the
sample size and the short duration of the trial. These results are
promising and warrant further investigation.
Discussion
The articles included in this review are an indication of the
growing interest in interventions for the prevention and treat-
ment of TSA in the adult oncology patients. Some methodo-
logical issues limited the study findings and thus reduced the
ability to compare study results. First, most of the studies in
this review had small samples drawn from populations where
TSAs were most common, limiting generalizability. The sam-
ples of the randomized control trials (RCT) included in this
review ranged from 12 to 107 participants [9, 10, 12, 13,
16–20]. The remaining studies had samples ranging from 8
to 851 participants [11, 14, 15]. Inadequate sample size ob-
scures differences between groups that may exist. Power cal-
culations were only reported for two studies, one at 85 % [10]
and the other at 90 % [20]. Power was not relevant in the trial
by Brisbois et al., as it was a proof-of-principle pilot trial [9],
and power was not discussed in the remaining studies [12, 13,
16–19]. Second, generalizability was reduced by the study of
specific populations; four studies included only individuals
with head and neck cancer [12, 15, 16, 20], and another study
limited recruitment to patients receiving docetaxel and pacli-
taxel [17]. Only three of the studies in this review were repre-
sentative of the general cancer population and various treat-
ment regimes [9, 10, 14]. Although there are merits to both
2847
approaches, generalizability is compromised with a homoge-
neous sample.
Blinding is a common strategy used to increase the
internal validity of a study. Patients were double blinded
in five of the RCT studies [9, 10, 12, 17, 20] in this
review and were blinded to treatment in one study [19].
It was unclear if the patients were blinded in the trial
by Yamagata et al. [18]. The patients were not blinded
in the remaining two RCTs [13, 16], and thus, partici-
pants’ responses may have been influenced by their
knowledge of whether they were receiving the experi-
mental treatment.
Factors such as study design, dose variations, mea-
surement approaches and primary end points influence
whether study results can be compared. The studies
included in this review used a variety of tools to assess
TSA. Although nine of the studies in this review were
randomized control trials [9, 10, 12, 13, 16–20], the
variables studied and measures used were not consis-
tent. The remaining studies included a prospective
follow-up study [15], and two studies that used quasi-
experimental designs with reported study lengths rang-
ing from 22 days to 8 months [11, 14].
We recommend that future researchers use an RCT design
with an adequate sample size and collect data using both val-
idated objective assessments and validated patient-reported
outcomes. This approach would ensure that the data includes
a more comprehensive view of participants’ experiences of
TSA. Potential confounders such as oral rinses, nutritional
supplements and variation in dosing should be controlled in
the analysis. Unfortunately, there are few studies on the path-
ophysiological features of TSA. Multidisciplinary research
teams are strongly urged to design their studies in ways that
make it possible to explore these underlying mechanisms.
These teams should also explore the importance of oral as-
sessment and the impact of oral hygiene on TSAs and study
outcomes. Based on the findings of this review, larger trials
evaluating the efficacy of marinol, megestrol acetate and
S. dulcificum as treatments of TSA are warranted.
Selection of a single intervention to alleviate TSAs is
limited by our lack of knowledge of the precise mech-
anisms causing TSAs. Suggested mechanisms include
treatment-associated damage to receptor cells and inter-
ference with neuronal activities, bitter and metallic sen-
sations from antineoplastic and other drugs, oral muco-
sitis, reduced taste cell regeneration due to zinc deple-
tion and unpleasant sensations generated by oral health
issues such as lack of oral hygiene and infections [1,
23, 24]. Further, sensory perception of a food is influ-
enced by all of its sensory properties, including texture,
appearance, and food presentation [25].
This review has several implications for practice and edu-
cation. Nurse practitioners are well established in oncology
2848 Support Care Cancer (2015) 23:2843–2851

multiple potential
Non-validated tool,
care in Alberta, but the scope and availability of nurse practi-

attrition details,
possible group

confounding
tioners varies among other jurisdictions. In some settings

Small sample,

Small sample,
differences

differences
Limitations

variables

(age), no
where nurse practitioners are not available, ordering these

group
medications would be the responsibility of the attending
physician. Regardless of who prescribes, decisions re-
garding interventions should be made in close collabo-

controlled dietary
ration with all members of the health care team. Nurses

Objective measures,
should be educated about TSA and taught simple strat-

Large treatment
Validated tool
egies for assessment that could be included in routine

Strengths

intake
effect
patient care, such as routinely asking patients if they
have noticed changes in taste or smell. Assessment of
TSA is critical because it may also be linked to other
common problems such as weight loss. If there are sig-

No adverse events
nificant changes in taste and smell, patients should be

related to MA
Adverse events

None reported

None reported
referred to a dietician for further evaluation and possible

reported
diet modifications. The multidisciplinary team should
also be encouraged to advise patients of the potential
for TSAs, as distress may be worse if such changes
are unexpected [6].

significant positive effect

acetate had a statistically

have positive effects on

did appear to provide
significant benefit to
Effective—zinc sulfate

administration may
Effective—megestrol
patients with TSA

Effective—IV zinc
Limitations

on TSA
Findings

TSA
This state-of-the-science review was limited to research pub-
lished in the last 20 years, which may have had an impact on
the interventions included and the conclusions that were
drawn. This review was also limited to interventions that were
within the scope of professional nursing practice and, thus,

lung cancer receiving

weight loss related to
Sample size Sample characteristics

their first course of

anorexia, TSA and

radiation treatment
cancer undergoing
excluded strategies such as limiting the size of the field during

Adults with primary

advanced cancer
Adult patients with

Adult patients with

head and neck

chemotherapy
radiation therapy.
experiencing
RT

Conclusions
Intervention

Intervention

Intervention
n = 50

n = 50

The purpose of the review was to provide a comprehensive

n=9

n=9

n=7

n=5
Control

Control

Control
Summary of methodological elements and findings

summary of studies on therapies and supportive strategies that

nurses could use to prevent or manage TSA experienced by
adult oncology patients. Nine interventions were identified
480 mg qd
45 mg po

day IV
0.33 mg/
regimen
Intervention/ Dosing

and examined. The most promising interventions are marinol,

tid

megestrol acetate and S. dulcificum, but future research with

larger samples are needed to confirm their efficacy. In the
prevention/

prevention
supportive
treatment

(MA) for
Oral zinc as

for TSA

meantime, nurses should ensure that patients are aware of

IV zinc for

of TSA
Megestrol

care of
acetate

TSA

the potential for TSA and should include assessment of TSA

goal

in their routine practice, given the potential links to other

adverse patient outcomes such as weight loss.
double-blind

control pilot
Study design

controlled

controlled
Ripamonti Randomized

Randomized

Yamagata Randomized
placebo-
trial

trial

trial
Appendix A

Table 1

Conflict of interest The authors declare that they have no competing

1998

2000

2003
et al.

et al.

et al.
Author

[12]

[19]

[18]
Erkurt

interests. The authors have full control of all primary data and permit the
year

journal to review the data if requested.

Table 1 (continued)

Author Study design Intervention/ Dosing Sample size Sample characteristics Findings Adverse events Strengths Limitations
year goal regimen

dosing different
from other trials
Buntzel Prospective Amifostine Unclear Intervention Adult patients with advanced Effective—amifostine Unclear Large treatment effect, Non-randomized,
et al. follow-up for n = 519 head and neck cancer who significantly reduced TSA sample size, duration poor
2007 study prevention Control received RCT alone or RCT in adult cancer patients of study generalizability,
[15] of TSA n = 332 with amifostine receiving RCT difference in
group size
Halyard Randomized Oral zinc for 45 mg po Intervention Adult patients with advanced Not effective—zinc sulfate Adverse events were Design sample size Non-validated tool,
et al. double-blind prevention/ tid, n = 36 head and neck cancer did not favourably affect rare with comparable some patients
Support Care Cancer (2015) 23:2843–2851

2007 phase III supportive 5 weeks Control undergoing RT the interval to taste frequencies and received
[20] control trial care of n = 47 recovery severity between the amifostine
TSA (169 at two groups
start, only
83
completed
the study)
Schiffman Randomized Teaching and Timing of Intervention Lung or breast cancer patients Effective, not all effects None reported Random, multiple High attrition, not
et al. control trial flavour interven n = 54 55–84 years receiving statistically significant— assessment points, blinded, not
2007 enhance tion Control chemotherapy flavour enhancement and multiple tools for generalizable to
[13] ment as an unclear n = 53 education may have a testing patients in poor or
interven positive effect on TSA declining health
tion for
TSA
Strasser Randomized Oral 30 g/day Intervention Adult cancer patients receiving Not effective—oral glutamine Statistically significant Random, multiple Small sample,
et al. double-blind glutamine n = 21 taxane-based chemotherapy did not prevent or decrease increase in nausea assessment points, not generalizable
2008 placebo- to prevent Control for the first time, with no TSA associated with and grade 2 objective and
[17] controlled TSA n = 20 prior surgery or RT of oral or taxane-based peripheral subjective testing
trial nasal region chemotherapy neuropathy in
glutamine group
Jham et al. Secondary Bethanechol 25 mg tid Intervention Adult patients with Not effective—bethanechol None reported Appropriate Small sample,
2009 analysis of a to prevent n = 16 advanced head and neck does not appear to reduce stratification and inconsistent
[16] randomized TSA Control cancer undergoing RT the incidence of TSA statistical cancer treatments
phase III n = 20 when given with RT analysis
prospective
trial
Rehwaldt Quasi- Education— Education n = 42 Heterogeneous sample of adult Effective 74–87 % of None reported High treatment effect, Small sample, short
et al. experimental strategies imple cancer patients who have had time—the teaching appropriate duration between
2009 pre/post to manage mented at least 2 doses of intervention was helpful for statistical analysis, data collection
[11] design TSA post- chemotherapy 74–87 % of respondents including analysis of points (2 weeks)
TSA group differences Confusing tool
Brisbois Phase II Marinol 2.5 mg bid Intervention Adult patients with advanced Effective—THC may be Most serious AE High treatment effect, Sample size
et al. randomized (THC) as a (n = 3, n = 24 cancer experiencing TSA not useful in treating TSA and unrelated, 4 unclear, low risk of bias, (results require
2011 double-blind treatment 2.5 mg Control on concurrent appetite increasing oral 1 possibly appropriate design verification in
[9] placebo- of TSA tid) n = 22 stimulants intake related (irregular larger trials) and
controlled heartbeat) duration
2849

pilot study
2850 Support Care Cancer (2015) 23:2843–2851

Participants trialled both Small sample, non-

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